Substantial evidence suggests that risk factors and therapeutic approaches derived from the study of Caucasians may not be accurate or effective when applied to individuals of differing ethnicity or race. Many Minority populations in the US, including African American women, have a markedly increased risk from obesity, diabetes mellitus, hypertension, cardiovascular disease, and mortality. This unit investigates the genetic, physiologic, metabolic, and behavioral factors involved in determining weight gain in African Americans and Caucasians. We have found that ACTH levels of African American women, men, and children following ovine CRH are two-fold higher than those of Caucasians, despite no differences in cortisol secretion, that visceral adipose tissue burden in obese African American women is significantly smaller than that of obese Caucasian women, and that less total abdominal, subcutaneous abdominal, and visceral adipose tissue in non-obese African American prepubertal girls than in Caucasian girls, findings that imply the relationship between visceral fat and the complications of obesity are different in African Americans and Caucasians. The susceptibility to weight gain in African American may also result from differences in metabolic efficiency: we have also found that resting energy expenditure is approximately 90 kcal/d less in African American than in Caucasian normal weight girls. Related to the significantly increased prevalence of non-insulin-dependent diabetes mellitus in African Americans compared with Caucasians, this unit has investigated differences in insulin sensitivity, glucose disposal, and fat cell metabolism. In normal weight children we have found a correlation of the subcutaneous adipose tissue depot with insulin levels before and after an oral glucose tolerance test only in African Americans. It is unknown whether these differences are found in obese children or in children at high risk for developing obesity. We will compare body composition, energy expenditure, insulin sensitivity and glucose disposal of obese African American and Caucasian prepubertal obese children and non-obese children of obese African American and Caucasian parents, in order to characterize the timing and nature of factors that may contribute to the prevalence of obesity and its complications. We will also relate serum levels of the body-fat related protein, leptin, to these measures, and characterize the role of the beta-3 adrenergic receptor and leptin signalling pathway in these children's obesity. We will then attempt to follow the growth of these children for the next 15 years. These studies will aid in the rational development of treatments for, and programs for the prevention of, obesity in minority populations.